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Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Mini-Review Article

Ramalin: A Multi-Mechanistic Lichen Metabolite of Pharmacological Importance

Author(s): Deepti Katiyar*, Priya Bansal, Abhishek Kumar and Surya Prakash

Volume 19, Issue 1, 2023

Published on: 19 August, 2022

Article ID: e240322202584 Pages: 7

DOI: 10.2174/1573407218666220324120229

Price: $65

Abstract

Background: Ramalin (γ-glutamyl-N'-(2-hydroxyphenyl) hydrazide), a nitrogencontaining lichen secondary metabolite, was isolated from Ramalina terebrata, an Antarctic lichen. Since then, it has attracted several researchers, thus leading to various research investigations exploring the pharmacological potential of Ramalin.

Methods: The bibliographic databases were explored for the peer-reviewed research related to the pharmacological importance of Ramalin.

Results: The article summarizes the antioxidant, anti-cancer, anti-obesity, antibacterial, and antiallergic activities of this molecule. Additionally, the studies conducted to show the potential of Ramalin in atherosclerosis, atopic dermatitis, neurodegenerative disorders, hepatic fibrosis and its role in autophagy suppression and enzyme inhibition are also described briefly. Moreover, the experimental findings also depict that Ramalin did not show any toxicity.

Conclusion: The current review shall be beneficial for future researchers interested in working on Ramalin because it summarizes all the relevant publications starting from its first-time isolation to the articles of 2021.

Keywords: Lichen, Ramalina terebrata, Ramalin, Anti-oxidant, Anti-cancer, Anti-inflammatorLichen, Anti-inflammatory

Graphical Abstract

[1]
Moreira, A.S.N.; Braz-Filho, R.; Mussi-Dias, V.; Vieira, I.J.C. Chemistry and biological activity of ramalina lichenized fungi. Molecules, 2015, 20(5), 8952-8987.
[http://dx.doi.org/10.3390/molecules20058952] [PMID: 25996207]
[2]
Huneck, S.; Yoshimura, I. Identification of lichen substances, 1st ed; Springer-Verlag: Berling, Heidelberg, 1996.
[http://dx.doi.org/10.1007/978-3-642-85243-5]
[3]
Boustie, J.; Grube, M. Lichens - A promising source of bioactive secondary metabolites. Plant Genet. Resour., 2005, 3(2), 273-287.
[http://dx.doi.org/10.1079/PGR200572]
[4]
White, P.A.S.; Oliveira, R.C.M.; Oliveira, A.P.; Serafini, M.R. Araújo, A.A.S.; Gelain, D.P.; Moreira, J.C.; Almeida, J.R.; Quintans, J.S.; Quintans-Junior, L.J.; Santos, M.R. Antioxidant activity and mechanisms of action of natural compounds isolated from lichens: A systematic review. Molecules, 2014, 19(9), 14496-14527.
[http://dx.doi.org/10.3390/molecules190914496] [PMID: 25221871]
[5]
Melo, M.G.D.; dos Santos, J.P.; Serafini, M.R.; Caregnato, F.F.; Pasquali, M.A.B.; Rabelo, T.K.; da Rocha, R.F.; Quintans, L., Jr Araújo, A.A.; da Silva, F.A.; Moreira, J.C.; Gelain, D.P. Redox properties and cytoprotective actions of atranorin, a lichen secondary metabolite. Toxicol. In-Vitro, 2011, 25(2), 462-468.
[http://dx.doi.org/10.1016/j.tiv.2010.11.014] [PMID: 21111802]
[6]
Cornejo, A.; Salgado, F.; Caballero, J.; Vargas, R.; Simirgiotis, M.; Areche, C. Secondary Metabolites in Ramalina terebrata Detected by UHPLC/ESI/MS/MS and identification of parietin as tau protein inhibitor. Int. J. Mol. Sci., 2016, 17(8), 1303.
[http://dx.doi.org/10.3390/ijms17081303] [PMID: 27548142]
[7]
Shukla, V.; Joshi, G.; Rawat, M.S.M. Lichens as a potential natural source of bioactive compounds: A review. Phytochem. Rev., 2010, 9(2), 303-314.
[http://dx.doi.org/10.1007/s11101-010-9189-6]
[8]
Molnár. K.; Farkas, E. Current results on biological activities of lichen secondary metabolites: A review. Z. Naturforsch. C J. Biosci., 2010, 65(3-4), 157-173.
[http://dx.doi.org/10.1515/znc-2010-3-401] [PMID: 20469633]
[9]
Basile, A.; Rigano, D.; Loppi, S.; Di Santi, A.; Nebbioso, A.; Sorbo, S.; Conte, B.; Paoli, L.; De Ruberto, F.; Molinari, A.M.; Altucci, L.; Bontempo, P. Antiproliferative, antibacterial and antifungal activity of the lichen Xanthoria parietina and its secondary metabolite parietin. Int. J. Mol. Sci., 2015, 16(4), 7861-7875.
[http://dx.doi.org/10.3390/ijms16047861] [PMID: 25860944]
[10]
Gausla, Y.; Ustvedt, E.M. Is parietin a UV-B or a blue-light screening pigment in the lichen Xanthoria parietina? Photochem. Photobiol. Sci., 2003, 2(4), 424-432.
[http://dx.doi.org/10.1039/b212532c] [PMID: 12760542]
[11]
Acharius, E. Lichenographia universalis, 1809, 122, 598.
[12]
Pandey, D.P.; Bhattarai, H.D. Ramalin, a novel phenyl hydrazide from the lichen Ramalina terebrata: Isolation, total synthesis and biological activities. Tribhuvan Univ. J., 2016, 30(2), 35-42.
[http://dx.doi.org/10.3126/tuj.v30i2.25544]
[13]
Fernández-Moriano. C.; Gómez-Serranillos, M.P.; Crespo, A. Antioxidant potential of lichen species and their secondary metabolites. A systematic review. Pharm. Biol., 2016, 54(1), 1-17.
[http://dx.doi.org/10.3109/13880209.2014.1003354] [PMID: 25885942]
[14]
Paudel, B.; Bhattarai, H.D.; Koh, H.Y.; Lee, S.G.; Han, S.J.; Lee, H.K.; Oh, H.; Shin, H.W.; Yim, J.H. Ramalin, a novel nontoxic antioxidant compound from the antarctic lichen Ramalina terebrata. Phytomedicine, 2011, 18(14), 1285-1290.
[http://dx.doi.org/10.1016/j.phymed.2011.06.007] [PMID: 21802926]
[15]
Vo, Q.V.; Tam, N.M.; Bay, M.V.; Mechler, A. The radical scavenging activity of natural ramalin: A mechanistic and kinetic study. Chem. Phys. Lett., 2019, 739, 137004.
[http://dx.doi.org/10.1016/j.cplett.2019.137004]
[16]
Brewer, M.S. Natural antioxidants: Sources, compounds, mechanisms of action, and potential applications. Compr. Rev. Food Sci. Food Saf., 2011, 10(4), 221-247.
[http://dx.doi.org/10.1111/j.1541-4337.2011.00156.x]
[17]
Kumar, A.; Jha, S.; Pattanayak, S.P. Daphnetin ameliorates 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis through Nrf-2-Keap1 and NF-κB pathways. Biomed. Pharmacother., 2016, 82, 439-448.
[http://dx.doi.org/10.1016/j.biopha.2016.05.028] [PMID: 27470383]
[18]
Kumar, A.; Sunita, P.; Jha, S.; Pattanayak, S.P. 7,8-Dihydroxycoumarin exerts antitumor potential on DMBA-induced mammary carcinogenesis by inhibiting ERα PR, EGFR, and IGF1R: Involvement of MAPK1/2-JNK1/2-Akt pathway. J. Physiol. Biochem., 2018, 74(2), 223-234.
[http://dx.doi.org/10.1007/s13105-018-0608-2] [PMID: 29435821]
[19]
Marques, J.M.M. Anticancer activity of lichen substances: A systematic review, Faculdade de Ciências da Saúde Universidade; Fernando Pessoa Porto, 2019, p. 1.
[20]
Suh, S.S.; Kim, T.K.; Kim, J.E.; Hong, J.M.; Nguyen, T.T.T.; Han, S.J.; Youn, U.J.; Yim, J.H.; Kim, I.C. Anticancer activity of ramalin, a secondary metabolite from the antarctic lichen Ramalina terebrata, against colorectal cancer cells. Molecules, 2017, 22(8), 1361.
[http://dx.doi.org/10.3390/molecules22081361] [PMID: 28817102]
[21]
Lee, E.; Lee, C.G.; Yim, J.H.; Lee, H.K.; Pyo, S. Ramalin-Mediated apoptosis is enhanced by autophagy inhibition in human breast cancer cells. Phytother. Res., 2016, 30(3), 426-438.
[http://dx.doi.org/10.1002/ptr.5544] [PMID: 26676298]
[22]
Park, B.; Lee, C.; Kim, P.S.; Pyo, S. The apoptotic effect of ramalin on human breast cancer cells. FASEB J., 2014, 28(S1), 657-11.
[http://dx.doi.org/10.1096/fasebj.28.1_supplement.657.11]
[23]
Kim, S.Y.; Jang, Y.J.; Park, B.; Yim, J.H.; Lee, H.K.; Rhee, D.K.; Pyo, S. Ramalin inhibits differentiation of 3T3-L1 preadipocytes and suppresses adiposity and body weight in a high-fat diet-fed C57BL/6J mice. Chem. Biol. Interact., 2016, 257, 71-80, 257.
[http://dx.doi.org/10.1016/j.cbi.2016.07.034] [PMID: 27481193]
[24]
Lee, H.; Lee, C.; Jang, Y.; Pyo, S. Ramalin suppresses adipocyte differentiation through the MAPKs pathway in 3T3-L1 preadipocyte. FASEB J., 2014, 28, 657-10.
[25]
Park, B.; Lee, C.; Jang, Y.; Pyo, S. Anti-obese effect of ramalin in high-fat diet-induced obese mice. The Faseb J. Nutrition, 2014, 28, 824-827.
[26]
Paudel, B.; Bhattarai, H.D.; Lee, H.K.; Oh, H.; Shin, H.W.; Yim, J.H. Antibacterial activities of ramalin, usnic acid and its three derivatives isolated from the antarctic lichen Ramalina terebrata. Z. Naturforsch. C J. Biosci., 2010, 65(1-2), 34-38.
[http://dx.doi.org/10.1515/znc-2010-1-206] [PMID: 20355318]
[27]
Park, H.J.; Yim, J.H.; Pyo, S. Ramalin inhibits LPS - induced NO release in macrophages by regulating MAPK and NF – κB activities. FASEB J., 2010, 24(S1), 966-6.
[http://dx.doi.org/10.1096/fasebj.24.1_supplement.966.6]
[28]
Park, B.; Yim, J.H.; Lee, H.K.; Kim, B.O.; Pyo, S. Ramalin inhibits VCAM-1 expression and adhesion of monocyte to vascular smooth muscle cells through MAPK and PADI4-dependent NF-kB and AP-1 pathways. Biosci. Biotechnol. Biochem., 2015, 79(4), 539-552.
[http://dx.doi.org/10.1080/09168451.2014.991681] [PMID: 25494680]
[29]
Jang, Y.J.; Pyo, S. Anti-allergic effect of ramalin from ramalina terebrata in TNF-α-stimulated HaCaT and RBL-2H3 cells. FASEB J., 2015, 29(S1), 593-14.
[http://dx.doi.org/10.1096/fasebj.29.1_supplement.593.14]
[30]
Park, H.J.; Byeon, H.E.; Koo, H.J.; Yim, J.H.; Lee, H.K.; Pyo, S. Protective effects of ramalin against atherosclerosis in ApoE-deficient mice. FASEB J., 2011, 25(S1), 1089-8.
[http://dx.doi.org/10.1096/fasebj.25.1_supplement.1089.8]
[31]
Park, B.; Rhee, D.K.; Pyo, S. The inhibitory effect of ramalin on the expression of VCAM-1 in human aortic smooth muscle cells. FASEB J., 2012, 26(S1), lb369-lb369.
[http://dx.doi.org/10.1096/fasebj.26.1_supplement.lb369]
[32]
Leung, D.Y.; Bieber, T. Atopic dermatitis. Lancet, 2003, 361(9352), 151-160.
[http://dx.doi.org/10.1016/S0140-6736(03)12193-9] [PMID: 12531593]
[33]
Park, H.J.; Jang, Y.J.; Yim, J.H.; Lee, H.K.; Pyo, S. Ramalin isolated from Ramalina Terebrata attenuates atopic dermatitis-like skin lesions in Balb/c mice and cutaneous immune responses in keratinocytes and mast cells. Phytother. Res., 2016, 30(12), 1978-1987.
[http://dx.doi.org/10.1002/ptr.5703] [PMID: 27558640]
[34]
Yim, J.H.; Kim, C.; Han, J.; Do, G.; Jo, D.G. Composition for preventing or treating neurodegenerative diseases. US009968576B2 2018.
[35]
Alt, Y.; Grimm, A.; Schlegel, L.; Grambihler, A.; Kittner, J.M.; Wiltink, J.; Galle, P.R. Wörns, M.A.; Schattenberg, J.M. The impact of liver cell injury on health-related quality of life in patients with chronic liver disease. PLoS One, 2016, 11(3), e0151200.
[http://dx.doi.org/10.1371/journal.pone.0151200] [PMID: 26990427]
[36]
Baiocchini, A.; Montaldo, C.; Conigliaro, A.; Grimaldi, A.; Correani, V.; Mura, F.; Ciccosanti, F.; Rotiroti, N.; Brenna, A.; Montalbano, M.; D’Offizi, G.; Capobianchi, M.R.; Alessandro, R.; Piacentini, M.; Schininà, M.E.; Maras, B.; Del Nonno, F.; Tripodi, M.; Mancone, C. Extracellular matrix molecular remodeling in human liver fibrosis evolution. PLoS One, 2016, 11(3), e0151736.
[http://dx.doi.org/10.1371/journal.pone.0151736] [PMID: 26998606]
[37]
Kim, M.K.; Kim, M.A.; Yim, J.H.; Lee, D.H.; Cho, S.K.; Yang, S.G. Ramalin, an antioxidant compound derived from antarctic lichen, prevents progression of liver fibrosis induced by dimethylnitrosamine (DNM) in rats. Biochem. Biophys. Res. Commun., 2018, 504(1), 25-33.
[http://dx.doi.org/10.1016/j.bbrc.2018.08.103] [PMID: 30172374]
[38]
Park, H.J.; Yim, J.H.; Lee, H.K.; Pyo, S. Ramalin inhibits LPS-induced autophagic response in macrophages through the downregulation of iNOS expression. FASEB J., 2013, 27(S1), 888-2.
[http://dx.doi.org/10.1096/fasebj.27.1_supplement.888.2]
[39]
Chang, Y.; Ryu, J.; Lee, S.; Park, S.G.; Bhattarai, H.D.; Yim, J.H.; Jin, M-H. Inhibition of melanogenesis by Ramalin from the Antarctic lichen, Ramalina terebrata. J. Soc.Cosmet. Scientists. Korea, 2012, 38(3), 247-254.
[http://dx.doi.org/10.15230/SCSK.2012.38.3.247]
[40]
Prashith Kekuda, T.R.; Lavanya, D.; Pooja, R. Lichens as promising resources of enzyme inhibitors: A review. J. Drug Deliv. Ther., 2019, 9(2-s), 665-676.

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